The neurodevelopmental disorders autism spectrum disorders (ASDs: autism) and Fragile X Syndrome (FXS) are childhood lifelong disorders that may result in marked impairment in social behavior, communication skills, and cognitive function. The severity of the symptoms exhibited by individual identified with these neurodevelopmental disorders vary widely. Unfortunately, many individual afflicted with these disorders exhibit profound symptoms some are unable to care for themselves while other exhibit greatly diminished capacity to function in society. While the cause of FXS is known the various neuronal pathways afflicted by this condition is unknown as are the levels of specific neuroactive compounds in the brains of these individual. With regard of idiopathic autistic disorder even the root cause of the disorder remains unknown. Because of the impact that these disorders have on those diagnosed with the disorder there is an intense amount of pre-clinical and clinical research devoted to developing treatments for these conditions. Despite the work devoted to diagnosing and treating there remains a pressing need for new therapies to help individuals afflicted with these disorders lead more comfortable and independent lives. The materials, methods, and systems disclosed herein are intended to address these vital needs.
Autism spectrum disorders are lifelong childhood-onset neurodevelopmental disorders causing marked impairment in social behavior and communication. According to the Department of Health & Human Services (DHHS), the rising prevalence of ASDs, currently estimated at 1 in 110 children, warrants ASDs being considered a national health emergency. Persons with ASD also frequently exhibit additional interfering symptoms such as aggression, self-injury, compulsions, inattention, hyperactivity, and anxiety among others. The costs of ASDs (estimated at $95 billion annually in the United States) to society is large and ever increasing. The presentation of autism is heterogeneous. For example, persons with autism may or may not have intellectual disability, seizures, or functional speech. This heterogeneity has made both research into the cause and effective treatment of ASDs challenging. An understanding of the cause of autism remains elusive with only approximately 10% of cases being associated with known genetic abnormalities. Regarding treatment, to date no drugs have been shown effective in large-scale trials to treat the core social and communication impairments of ASDs. The heterogeneity of autism has led to many promising drug treatments failing large-scale trials due to difficulty identifying appropriate subgroups for testing. Given such variable presentation, rationale drug development in autism will need to focus on defining appropriate subgroups where drug benefit is maximized. Biomarker development in autism presents a unique opportunity to address these challenges of therapeutic development. The 2011 Strategic Plan of the Department of Health & Human Services Interagency Autism Coordinating Committee strongly emphasized the need for autism biomarker development given the potential of biomarkers to provide early disease detection, assessment of illness severity, indicators of pharmacological response, and the ability to utilize biomarkers to identify subgroups within autism for targeted treatment development.
Given the heterogeneity of autism, known causes of autism provide the best foundation for pharmacotherapy and biomarker development. Among these known causes, recent research findings in Fragile X Syndrome (FXS) combined with the status of FXS as the most common single gene cause of autism make this disorder a prime candidate upon which to develop an autism therapeutics development strategy. FXS is the most common inherited form of developmental delay impacting 1 in 4,000 persons. Two in three persons with FXS also suffer from autism and overall FXS accounts for 5-7% of all autism cases.
To date, no drug has been approved by the United States Food and Drug Administration (FDA) for reducing the core social impairment of autistic disorder. Many pharmacotherapy trials in autism targeting social impairment have yielded uniformly negative results. Accordingly, there is need for materials and methods for treating these conditions. Some aspects of the instant disclosure provide materials and methods for the study, diagnoses, and treatment of idiopathic and Fragile X Syndrome (FXS) linked Autism Spectrum Disorder (ASD).